The proposed studies are designed to analyze the effects of Purkinje terminal degeneration on target cells in the deep nuclei. The animals to be used are four types of neurological mutant mice featuring Purkinje cell loss occurring during four different stages of cerebellar development. Extent of loss is total in one mutant and partial in others. These animals can be compared with a granule cell deficient mutant in which deep nuclei are not affected as well as with experimentally decorticate animals. The questions asked are about the response of the deep nuclei to removal of its dense GABA releasing afferent pathway under the varied circumstances represented in these animals. The time course and extent of decrease in GABA and its synthesizing enzyme will be determined to: 1) learn how much of the deep nuclear content of these substances is localized to Purkinje terminals, 2) look for redistribution after Purkinje terminal degeneration, 3) see if the surviving Purkinje axons can sprout under conditions of partial denervation of deep nuclei. Cellular localization of GABA will be studied using 3H GABA autoradiography in normal and mutant tissue. The fate of GABA receptors in the denervated region will be examined using sodium independent binding of 3H GABA as a measure of receptor concentration and autoradiography of 3H muscimol to localize receptor in tissue sections. The normal concentration and location of GABA receptor will be established first. Then receptor concentration and localization will be examined in denervated tissue. The ontogenetic development of receptor in deep nuclei will be studied under conditions of early and late denervation. The effects of full and of partial denervation on the development and fate of GABA receptor will be followed.